Timing of low tidal volume ventilation and intensive care unit mortality in acute respiratory distress syndrome. A prospective cohort study

Abstract

Rationale: Reducing tidal volume decreases mortality in acute respiratory distress syndrome (ARDS). However, the effect of the timing of low tidal volume ventilation is not well understood.

Objectives: To evaluate the association of intensive care unit (ICU) mortality with initial tidal volume and with tidal volume change over time.

Methods: Multivariable, time-varying Cox regression analysis of a multisite, prospective study of 482 patients with ARDS with 11,558 twice-daily tidal volume assessments (evaluated in milliliter per kilogram of predicted body weight [PBW]) and daily assessment of other mortality predictors.

Measurements and main results: An increase of 1 ml/kg PBW in initial tidal volume was associated with a 23% increase in ICU mortality risk (adjusted hazard ratio, 1.23; 95% confidence interval [CI], 1.06-1.44; P = 0.008). Moreover, a 1 ml/kg PBW increase in subsequent tidal volumes compared with the initial tidal volume was associated with a 15% increase in mortality risk (adjusted hazard ratio, 1.15; 95% CI, 1.02-1.29; P = 0.019). Compared with a prototypical patient receiving 8 days with a tidal volume of 6 ml/kg PBW, the absolute increase in ICU mortality (95% CI) of receiving 10 and 8 ml/kg PBW, respectively, across all 8 days was 7.2% (3.0-13.0%) and 2.7% (1.2-4.6%). In scenarios with variation in tidal volume over the 8-day period, mortality was higher when a larger volume was used earlier.

Conclusions: Higher tidal volumes shortly after ARDS onset were associated with a greater risk of ICU mortality compared with subsequent tidal volumes. Timely recognition of ARDS and adherence to low tidal volume ventilation is important for reducing mortality. Clinical trial registered with www.clinicaltrials.gov (NCT 00300248).

Trial registration: ClinicalTrials.gov NCT00300248.

Keywords: acute lung injury; artificial respiration; prospective studies; tidal volume.

Figure 1.

Flow of patients through study. ARDS = acute respiratory distress syndrome.

Figure 2.

Timing and direction of first change in tidal volume from initial ventilator setting after ARDS onset. The numbers of patients with their first tidal volume after ARDS onset of ≤6.5 and >6.5 ml/kg PBW, respectively, were 154 and 328. The data represented by the dots and connecting line represent the proportion of patients with tidal volume ≤6.5 ml/kg PBW, calculated based on the number of patients at that point in time that were alive and receiving mechanical ventilation with a measurable tidal volume. In patients with their first tidal volume >6.5 ml/kg, 17% had no change in tidal volume or an increase in tidal volume over all subsequent mechanical ventilator settings, whereas 39% had a decrease in the next ventilator setting with 78% ever having a decrease in tidal volume over all subsequent mechanical ventilator settings. ARDS = acute respiratory distress syndrome; PBW = predicted body weight.

Figure 3.

Kaplan-Meier survival curves for increase versus decrease in tidal volume from initial ventilator setting after ARDS onset. The numbers of patients with their first tidal volume after ARDS onset ≤6.5 and >6.5 ml/kg PBW, respectively, were 154 and 328. For patients with first tidal volume >6.5 ml/kg PBW, a subsequent decrease (vs. increase) in tidal volume was associated with significant improvement in survival as illustrated by the Kaplan-Meier survival curves and the log-rank test (P = 0.008). For patients with first tidal volume ≤6.5 ml/kg PBW, a subsequent decrease (vs. increase) in tidal volume was not associated with a significant difference in survival (P = 0.446). ARDS = acute respiratory distress syndrome; PBW = predicted body weight.